DESCRIPTION: Major depression in diabetes is a prevalent condition associated with an increased risk of diabetes complications. The investigators recently proved that short-term treatment of depression with antidepressants in diabetes is effective. Medication was not continued beyond the point of depression remission and, unfortunately, depression recurred in approximately 60 percent of patients within 1st year. Only eight percent remained euthymic over a 5-year follow-up period. Depression in diabetes has also been associated in cross- sectional studies with poor glycemic control, presumably an important intermediate in its association with complications. It is not known whether maintenance depression-treatment strategies increasingly employed in medically well subjects would be effective in diabetes, either to reduce depression recurrences or influence the long-term course of glycemic control. The investigators propose a longitudinal, two-site, two-phase (participation <18 months), controlled treatment outcome study in patients with non insulin dependent diabetes mellitus (NIDDM): 1) to determine if emerging practices for preventing depression recurrences in nondiabetic subjects should be applied to this medically ill group, and 2) to prospectively determine the inter-relationship of depression and glycemic control. In the open-label phase of the study, 262 depressed NIDDM patients will be treated with sertraline; 156 of these patients are expected to achieve recovery from depression and be assigned randomly to continued pharmacotherapy (n=78) or to placebo (n =78) and followed for a period up to 14 months. Survival methods will be used to determine the efficacy of maintenance pharmacotherapy; a comprehensive set of outcome measures will be used to determine the benefits of remaining depression-free in terms of compliance with diabetes treatment, social and occupational functioning, global well- being, and quality of life. Repeated measures ANCOVA and longitudinal modeling of mood and glycemia will be used to determine the benefits of maintenance sertraline and euthymia on glycemic control. The investigators hypothesize: 1) that maintenance pharmacotherapy for depression in diabetes will produce superior results on multiple depression and psychosocial outcome measures; 2) that depression and glycemic control covary in longitudinal follow-up; and 3) that maintenance antidepressant therapy will produce durable improvements in glycemic control and attenuate depression symptoms in response to hyperglycemia. In short, they expect that maintenance antidepressant treatment in diabetes will prevent or delay depression recurrence, promote durable improvements in glycemic control, and interrupt the vicious cycling of depression and glucose dysregulation.